全身及鞘内注射吗啡对大鼠神经病理性疼痛 spared 神经损伤模型的抗痛觉过敏作用

Antiallodynic effects of systemic and intrathecal morphine in the spared nerve injury model of neuropathic pain in rats.

作者信息

Zhao Chengshui, Tall Jill M, Meyer Richard A, Raja Srinivasa N

机构信息

Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

出版信息

Anesthesiology. 2004 Apr;100(4):905-11. doi: 10.1097/00000542-200404000-00021.

DOI:10.1097/00000542-200404000-00021

PMID:15087626

Abstract

BACKGROUND

The efficacy of opioids for neuropathic pain remains controversial. The effects of morphine on pain behavior were investigated in two animal models of neuropathic pain: the spared nerve injury (SNI) model and the spinal nerve ligation (SNL) model.

METHODS

Nerve injuries were created in rats either by tight ligation and section of the left tibial and common peroneal nerves (SNI) or by unilateral ligation of L5 and L6 spinal nerves (SNL). Paw withdrawal threshold to mechanical stimuli was measured using the up-down method in the hairy and glabrous skin territories of the sural nerve for SNI rats or in the mid-plantar paw of SNL rats.

RESULTS

Before SNI, the median paw withdrawal thresholds in hairy and glabrous skin were similar (26 g [25%, 75% quartiles: 26, 26 g]). The paw withdrawal threshold decreased after SNI in both hairy and glabrous skin (P < 0.001). Thirty days after the SNI, the threshold in hairy skin (0.3 g) was significantly lower than in glabrous skin (1.9 g; P < 0.001). In blinded experiments, both subcutaneous and intrathecal morphine (0.1-10 microg) dose-dependently attenuated mechanical allodynia induced by SNI measured in the hairy skin, an effect that was naloxone reversible. The ED50 for the intrathecal morphine was 0.52 microg (95% confidence interval, 0.31-0.90 microg). Morphine (1 microg intrathecal) attenuated SNI-induced mechanical allodynia in glabrous skin with potency similar to that in hairy skin. In SNL rats, morphine (30 microg intrathecal) almost completely reversed the SNL-induced mechanical allodynia.

CONCLUSIONS

(1) SNI-induced mechanical allodynia is characterized by a lower paw withdrawal threshold in hairy versus glabrous skin; (2) systemic and intrathecal morphine reverse SNI-induced mechanical allodynia in a dose-dependent fashion; and (3) intrathecal morphine also reverses SNL-induced mechanical allodynia. These results suggest that intrathecal opioids are likely to be effective in the treatment of neuropathic pain.

摘要

背景

阿片类药物治疗神经性疼痛的疗效仍存在争议。在两种神经性疼痛动物模型中研究了吗啡对疼痛行为的影响： spared神经损伤（SNI）模型和脊髓神经结扎（SNL）模型。

方法

通过紧密结扎并切断大鼠左侧胫神经和腓总神经（SNI）或单侧结扎L5和L6脊髓神经（SNL）来造成神经损伤。对于SNI大鼠，使用上下法测量在腓肠神经的有毛和无毛皮肤区域对机械刺激的爪退缩阈值；对于SNL大鼠，则测量足底中部的爪退缩阈值。

结果

在SNI之前，有毛和无毛皮肤的爪退缩阈值中位数相似（26克[四分位数间距：25%，75%为26，26克]）。SNI后，有毛和无毛皮肤的爪退缩阈值均降低（P<0.001）。SNI后30天，有毛皮肤的阈值（0.3克）显著低于无毛皮肤（1.9克；P<0.001）。在盲法实验中，皮下和鞘内注射吗啡（0.1 - 10微克）均剂量依赖性地减轻了在有毛皮肤中测量的由SNI诱导的机械性异常性疼痛，该效应可被纳洛酮逆转。鞘内注射吗啡的ED50为0.52微克（95%置信区间，0.31 - 0.90微克）。吗啡（鞘内注射1微克）减轻了SNI诱导的无毛皮肤机械性异常性疼痛，效力与有毛皮肤相似。在SNL大鼠中，吗啡（鞘内注射30微克）几乎完全逆转了SNL诱导的机械性异常性疼痛。